Scientists Develop Protein That Blocks Both Strains of HIV

Arguably the most exciting news from the world of HIV science since PrEP and treatment as prevention (TasP), is that scientists at The Scripps Research Institute in Florida have developed a protein so powerful it blocks against every strain of HIV-1 and HIV-2, even the meanest ones.

The discovery stems from what has increasingly become part of the HIV vernacular most associated with hope: CCR5. HIV can’t get in and hijack CD4 cells without help from the CCR5 receptor. In recent years, particularly since Timothy Ray Brown (aka “The Berlin Patient”) became the only person on earth ever cured of HIV, gene therapies focusing on the CCR5 receptor have begun to show great promise.

The new protein created by Scripps, eCD4-lg has demonstrated such potency it may even work as an unconventional vaccine. The anti-HIV agent, dubbed eCD4-lg, is “fused to a sulfopeptide mimicking CCR5,” the editors of the scientific report published this week in Nature explain. The protein “avidly binds the Env protein of HIV-1 and irreversibly inactivates it.”

In other words, HIV becomes locked out.

The research was published a year ago. The Scripps team led by Michael Farzan recently received $6 million from the Bill and Melinda Gates Foundation to keep their work going. “Farzan brings an innovative approach to combating HIV,” the website R&D reported. “The approach works by coaxing muscle cells into producing inhibitor proteins that block key sites on the virus’s surface used to attach and invade human immune cells—fooling the virus into thinking it is binding to a human cell. Unable to attach to cells, and unable to reproduce, the virus simply floats impotently in the blood stream.”

In a news release by Scripps last year, Farzan said, “Our compound is the broadest and most potent entry inhibitor described so far. Unlike antibodies, which fail to neutralize a large fraction of HIV-1 strains, our protein has been effective against all strains tested, raising the possibility it could offer an effective HIV vaccine alternative.”

Progress on an HIV vaccine using broadly neutralizing antibodies, or BnABs, has been slow and only has produced modest results in monkeys. Gene therapy approaches that focus on the CCr5 receptor have tended to lead to more exciting headlines.

One company already pursuing a gene therapy treatment in clinical trials for people already infected with HIV is Calimmune Inc.

“By reducing CCR5 expression and preventing HIV viral fusion, Cal-1 may protect the treated cells against HIV and has the potential to provide a continuous means of controlling HIV after a single treatment,” Calimmune announced in a news release last May after a very small trial where four volunteers were infused with their own blood stem cells.

The approach was shown to be effective in a test tube prior to clinical trials. Whether Cal-1 has proven effective in human clinical trials has yet to be announced. The therapy still is being assessed primarily for safety. A company spokesman told John Farrell, a writer for Forbes, that results may be disclosed prior to the conclusion of the trial in September. Farrell called Calimmune a company “definitely a company to keep an eye on in 2016.”

Strategies targeting CCR5 in immune therapy have flourished after Timothy Ray Brown, also known as “The Berlin Patient,” became the first person on earth ever to be functionally cured of HIV. Brown had acute myeloid leukemia as well as HIV. His leukemia was cured after receiving an allogenic stem cell transplant from a donor with a CCR5 delta 32 mutation. People who are homozygous (meaning the same two alleles on a gene) for CCR5 delta 32 are resistant to HIV.

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